The erythropoietin and regenerative medicine: a lesson from fish.

Erythropoietin (EPO), the main haematopoietic growth factor for the proliferation and differentiation of erythroid progenitor cells, is also known for its angiogenic and regenerative properties. In our research we demonstrated the regenerative effects of EPO administration in an experimental model of sea bass (Dicentrarchus labrax) subjected to amputation of the caudal fin. EPO-treated fish (3000 UI of human recombinant EPO-alpha) show an increased growth rate of their fins compared to those untreated. By analyzing fin length at established times (15 and 30 days after cut), EPO-treated fish always show an increased length compared to untreated ones. Moreover, exogenous EPO administration induces an enormous increase in EPO-blood levels at each observation time whereas these levels remained quite unmodified in untreated fishes. Immunochemical analyses performed by confocal laser scanning microscopic observations show an increased expression of EPO-receptors and PECAM-1 (an endothelial surface marker of vessels sprout) in the regenerating tissue, whereas no signs of inflammation or fi- brosis are recognizable. All these findings confirm EPO as a new factor involved in regenerative processes, also suggesting a potential, future utility for new therapeutical applications in the field of human regenerative medicine.